Pan‐cancer clinical and molecular analysis of racial disparities

Abstract

Background Racial disparities in cancer outcomes are increasingly recognized, but comprehensive analyses, including molecular studies, are limited. The objective of the current study was to perform a pan‐cancer clinical and epigenetic molecular analysis of outcomes in African American (AA) and European American (EA) patients. Methods Cross‐platform analyses using cancer databases (the Surveillance, Epidemiology, and End Results program database and the National Cancer Data Base) and a molecular database (The Cancer Genome Ancestry Atlas) were performed to evaluate clinical and epigenetic molecular differences between AA and EA patients based on genetic ancestry. Results In the primary pan‐cancer survival analysis using the Surveillance, Epidemiology, and End Results database (2,045,839 patients; 87.5% EA and 12.5% AA), AA patients had higher mortality rates for 28 of 42 cancer types analyzed (hazard ratio, >1.0). AAs continued to have higher mortality in 13 cancer types after adjustment for socioeconomic variables using the National Cancer Database (5,150,023 patients; 11.6% AA and 88.4% EA). Then, molecular features of 5,283 tumors were analyzed in patients who had genetic ancestry data available (87.2% EA and 12.8% AA). Genes were identified with altered DNA methylation along with increased microRNA expression levels unique to AA patients that are associated with cancer drug resistance. Increased miRNAs (miR‐15a, miR‐17, miR‐130‐3p, miR‐181a) were noted in common among AAs with breast, kidney, thyroid, or prostate carcinomas. Conclusions The current results identified epigenetic features in AA patients who have cancer that may contribute to higher mortality rates compared with EA patients who have cancer. Therefore, a focus on molecular signatures unique to AAs may identify actionable molecular abnormalities.

Histopathologic, Genetic and Molecular Characterization of Endometrial Cancer Racial Disparity

“…Histology alone, however, does not account for the worse survival of Black endometrial cancer patients. A study of data from the Surveillance, Epidemiology and End Results (SEER) program showed that Black in comparison with White patients had worse survival in every histologic category, stratified by stage, grade and age [ 16 , 22 ]. This study also found that rare aggressive tumor types accounted for a higher percentage of the deaths in Black (53%) compared with White (36%) patients.…”

“…Pathway analysis of the SEER program database from 2000 to 2015 in patients classified as European-American or African-American was performed to determine the clinical significance and biologic functions of the differentially expressed miRNAs related to cancer type [ 22 ]. They reported that differentially expressed miRNAs were associated with cancer drug resistance pathways through cancer drug efflux for all cancer types including uterine.…”

Exosomal miR‑130a‑3p promotes the progression of differentiated thyroid cancer by targeting insulin‑like growth factor 1

“…The main focus of the present study was miR-130a-3p, which has been found to be differentially expressed in different tumors, including breast cancer and non-small cell lung cancer ( 11 , 12 ). In addition, increased miR-130-3p levels have also been found in TC tissues ( 13 ). However, whether miR-130-3p is dysregulated in the exosomes of patients with DTC has yet to be reported.…”

Ancestry-associated transcriptomic profiles of breast cancer in patients of African, Arab, and European ancestry

“…To address this, several studies investigated molecular differences within TNBC tumors of African-American and European-American patients. TNBC tumors of African-American women were shown to display enrichment of gene sets related to a high proliferative rate, high genomic grade index, BRCA1 deficiency, increased activation of insulin-like growth factor 1 receptor, and increased angiogenesis, closely resembling the basal like-1 TNBC subtype gene signature as described by Lehmann et al 23,[28][29][30][31][32][33] . In addition, it has been suggested that an abundance of cancer stem cells might, in part, contribute to the worse survival of African-American women with TNBC tumors [34][35][36][37][38] .…”